Biology subjects

Gheres, K. W.

Publications and source records attributed to Gheres, K. W..

4 recordsLinked to original sources

bioRxiv2023

Low-intensity pulsed ultrasound stimulation (LIPUS) modulates microglial activation following intracortical microelectrode implantation.

Microglia are important players in surveillance and repair of the brain. Their activation mediates neuroinflammation caused by intracortical microelectrode implantation, which impedes the application of intracortical brain-computer interfaces (BCIs). While low-intensity pulsed ultrasound stimulation (LIPUS) can attenuate microglial activation, its potential to modulate the microglia-mediated neuroinflammation and enhance the bio-integration of microelectrodes remains insufficiently explored. We found that LIPUS increased microglia migration speed from 0.59{+/-}0.04 to 1.35{+/-}0.07 {micro}m/hr on day 1 and enhanced microglia expansion area from 44.50{+/-}6.86 to 93.15{+/-}8.77 {micro}m2/min on day 7, indicating improved tissue healing and surveillance. Furthermore, LIPUS reduced microglial activation by 17% on day 6, vessel-associated microglia ratio from 70.67{+/-}6.15 to 40.43{+/-}3.87% on day 7, and vessel diameter by 20% on day 28. Additionally, microglial coverage of the microelectrode was reduced by 50% in week 1, indicating better tissue-microelectrode integration. These data reveal that LIPUS helps resolve neuroinflammation around chronic intracortical microelectrodes.

bioengineering↗

bioRxiv2023

Arousal state transitions occlude sensory-evoked neurovascular coupling in neonatal mice

In the adult sensory cortex, increases in neural activity elicited by sensory stimulation usually drives vasodilation mediated by neurovascular coupling. However, whether neurovascular coupling is the same in neonatal animals as adults is controversial, as both canonical and inverted responses have been observed. We investigated the nature of neurovascular coupling in unanesthetized neonatal mice using optical imaging, electrophysiology, and BOLD fMRI. We find in neonatal (postnatal day 15, P15) mice, sensory stimulation induces a small increase in blood volume/BOLD signal, often followed by a large decrease in blood volume. An examination of arousal state of the mice revealed that neonatal mice were asleep a substantial fraction of the time, and that stimulation caused the animal to awaken. As cortical blood volume is much higher during REM and NREM sleep than the awake state, awakening occludes any sensory-evoked neurovascular coupling. When neonatal mice are stimulated during an awake period, they showed relatively normal (but slowed) neurovascular coupling, showing that that the typically observed constriction is due to arousal state changes. These result show that sleep-related vascular changes dominate over any sensory-evoked changes, and hemodynamic measures need to be considered in the context of arousal state changes. Significance StatementIn the adult brain, increases in neural activity are often followed by vasodilation, allowing activity to be monitored using optical or magnetic resonance imaging. However, in neonates, sensory stimulation can drive vasoconstriction, whose origin was not understood. We used optical and magnetic resonance imaging approaches to investigate hemodynamics in neonatal mice. We found that sensory-induced vasoconstriction occurred when the mice were asleep, as sleep is associated with dilation of the vasculature of the brain relative to the awake state. The stimulus awakens the mice, causing a constriction due to the arousal state change. Our study shows the importance of monitoring arousal state, particularly when investigating subjects that may sleep, and the dominance arousal effects on brain hemodynamics.

neuroscience↗

bioRxiv2020

Origins of 1/f-like tissue oxygenation fluctuations in the murine cortex

The concentration of oxygen in the brain spontaneously fluctuates, and the power distribution in these fluctuations has 1/f-like dynamics. Though these oscillations have been interpreted as being driven by neural activity, the origins of these 1/f-like oscillations is not well understood. Here, to gain insight of the origin of the 1/f-like oxygen fluctuations, we investigated the dynamics of tissue oxygenation and neural activity in awake behaving mice. We found that oxygen signal recorded from the cortex of mice had 1/f-like spectra. However, band-limited power in the local field potential, did not show corresponding 1/f-like fluctuations. When local neural activity was suppressed, the 1/f-like fluctuations in oxygen concentration persisted. Two-photon measurements of erythrocyte spacing fluctuations ( stalls) and mathematical modelling show that stochastic fluctuations in erythrocyte flow and stalling could underlie 1/f-like dynamics in oxygenation. These results show discrete nature of erythrocytes and their irregular flow, rather than neural activity, could drive 1/f-like fluctuations in tissue oxygenation.

neuroscience↗

bioRxiv2020

Neurovascular coupling and bilateral connectivity during NREM and REM sleep

Hemodynamic signals in the brain are used as surrogates of neural activity, but how these hemodynamic signals depend on arousal state is poorly understood. Here, we monitored neural activity and hemodynamic signals in un-anesthetized, head-fixed mice to understand how sleep and awake states impact cerebral hemodynamics. In parallel with electrophysiological recordings, we used intrinsic optical signal imaging to measure bilateral changes in cerebral hemoglobin ([HbT]), and two-photon laser scanning microscopy (2PLSM) to measure dilations of individual arterioles. We concurrently monitored body motion, whisker movement, muscle EMG, cortical LFP, and hippocampal LFP to classify the arousal state of the mouse into awake, NREM sleep, or REM sleep. We found that mice invariably fell asleep during imaging, and these sleep states were interspersed with periods of awake. During both NREM and REM sleep, mice showed large increases in [HbT] relative to the awake state, showing increase in hemoglobin and arteriole diameter two to five times larger than those seen in response to sensory stimulation. During NREM sleep, the amplitude of bilateral low-frequency oscillations in [HbT] increased markedly, and coherency between neural activity and hemodynamic signals was higher than the awake resting and REM states. Bilateral correlations in neural activity and [HbT] were highest during NREM sleep, and lowest in the awake state. Our results show that hemodynamic signals in the cortex are strongly modulated by arousal state, with hemodynamic changes during sleep being substantially larger than sensory-evoked responses. These results underscore the critical importance of behavioral monitoring during studies of spontaneous activity, as sleep-related hemodynamics dominate measures of neurovascular coupling and functional connectivity.

neuroscience↗